Noise is an important environmental stress factor in all industrialized societies, and a lot of adverse reactions have been described. Mental stress has been shown to produce intestinal disease, but the effects of noise stress, per se, on intestinal function, have not been investigated. Our preliminary studies demonstrate that housing rats in high activity room causes disruption of the intestinal epithelial barrier. A survey of the literature reveals that reactive oxygen species (ROS) may make an important contribution to disease pathology in inflammatory bowel disease (IBD), but their exact role has not been determined. The purpose of this study is to test the hypothesis that noise stress causes increased concentrations of ROS in mesenteric and intestinal tissue, and that the ROS produce venular leakage and epithelial disruption. Rats will be subjected to short period of noise during the day for 3 weeks. Control rats will be housed under similar conditions but without excess noise, and a third group of rats will be used to determine the extent of recovery. In all experiments, blood samples will be taken for analysis of superoxide radical (O2-) and hydrogen peroxide (H2O2). Experiments on Group 1 rats will be repeated in the presence of ROS scavengers for all aims. the Specific Aims will be as follows: 1) Relative concentrations of superoxide radical in the mesenteric tissue will be quantified in all 3 groups, using histological staining techniques. (2) Venular endothelial leakage, disruption of the endothelial cytoskeleton, and connective tissue mast cell degranulation in the mesentery will be evaluated in all 3 groups using epifluorescence microscopy and histological stains. 3) Relative concentrations of superoxide radical in intestinal mucosal tissue will be quantified in all 3 groups using staining techniques. 4) The intestinal mucosa will be fixed for light and electron microscopy in order to assess epithelial disruption and alterations in endothelial fenestrae. Mucosal mast cell degranulation will be evaluated, and activation of T-lymphocytes will be assessed by immunocytochemistry. Experiments will be performed on all 3 groups. With regard to future plans to extrapolate our findings to humans, epidemiologist, Dr. Michael Lebowitz, Ph.D., will act as a consultant to advise us on appropriate tests which may be performed on humans, and to determine suitable patient populations.